Modern diagnosis and classification of lymphoid cancers has relied on techniques such as immunohistochemistry, cytogenetics, fluorescence in situ hybridization, flow cytometry, and molecular genetics. However, these standard procedures and classification schemes have been challenged by newer gene sequencing techniques.

As cancer is caused by mutations in key cancer-specific genes, the ability to sequence patients’ genes has the potential to add unique diagnostic, prognostic, and predictive value to current strategies.

Next-generation gene sequencing technologies, which requires sequencing of the entire genome, have been extensively used in specific diseases to identify mutations and advance personalized medicine.

However, compared to genome-wide sequencing, targeted cancer sequencing panels that are focused on specific genes or gene regions with known associations with cancer can lead to quick detection of a variety of mutations using a single assay.

There are two methods that are commonly used for gene sequencing panels, which include capture hybridization-based sequencing and amplicon-based sequencing. While amplicon-based sequencing has been used often because it requires short preparation time and a small amount of DNA, capture sequencing has intrigued researchers due to its high testing accuracy.

Researchers from the University of British Columbia set out to determine the optimal targeted sequencing platform for detection of mutations in lymphoid cancer. Their aim was to accurately detect the full spectrum of mutations in the gene panel using tumor samples from lymphoma patients.

To do this, researchers developed a pipeline that consisted of a 32-gene panel that could accurately detect mutations associated with the most common lymphoid cancers, including chronic lymphocytic leukemia, diffuse large B-cell lymphoma, and follicular lymphoma. The genes were chosen by a six-person group of hematopathologists, clinician-oncologists, and translational scientists.

Results showed that capture hybridization-based sequencing is a superior method to amplicon sequencing as it had better, more uniform coverage and higher sensitivity for identification of mutations.

Furthermore, the gene panel that the researchers developed identified at least one mutation in 91 percent of tumors from 219 lymphoma patients. The assay was also able to determine subtype-specific mutation patterns and frequencies that were consistent with those previously known in published studies.

“This pipeline is an accurate and sensitive method for identifying actionable gene mutations in routinely acquired biopsy materials, suggesting further assessment of capture-based assays in the context of personalized lymphoma management,” the investigators concluded.

Lymphoma News Today

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